Deck 15: Genomes and Genomics

Question 1

James sees an online ad for an at-home genetic test that promises to deliver personalized nutritional advice based on an individual's genetic profile. The company can test for genetic variations, the advertisement states, that predispose individuals to developing health conditions such as heart disease and bone loss or that affect how they metabolize certain foods. If such variations are detected, the company can provide specific nutritional advice that will help counteract their effects. Always keen to take any steps available to ensure the best possible health for their family, James and his wife (Sally) decide that they both should be tested, as should their 11-year-old daughter (Patty). They order three kits.
Once the kits arrive, the family members use cotton swabs to take cell samples from their cheeks and place the swabs in individually labeled envelopes. They mail the envelopes back to the company, along with completed questionnaires regarding their diets. Four weeks later, they receive three individual reports detailing the test results and providing extensive guidelines about what foods they should eat. Among the results is the finding that James has a particular allele in a gene that may make him vulnerable to the presence of free radicals in his cells. The report suggests that he increase his intake of antioxidants, such as vitamins C and E, and highlights a number of foods that are rich in those vitamins. The tests also show that Sally has several genetic variations that indicate that she may be at risk for elevated bone loss. The report recommends that she try to minimize this possibility by increasing her intake of calcium and vitamin D and lists a number of foods she could emphasize in her diet. Finally, the report shows that Patty has a genetic variation that may mean that she has a lowered ability to metabolize saturated fats, putting her at risk for developing heart disease. The report points to ways in which she can lower her intake of saturated fats and lists various types of foods that would be beneficial for her.
A number of companies now offer genetic-testing services, promising to deliver personalized nutritional or other advice based on people's genetic profiles. Generally, these tests fall into two different categories, with individual companies offering unique combinations of the two. The first type of test detects alleles of known genes that encode proteins that play an established role in, for example, counteracting free radicals in cells or in building up bone. In such cases, it is easy to see why individuals carrying alleles that may encode proteins with lower levels of activity may be more vulnerable to free radicals or more susceptible to bone loss.
A second type of test examines genetic variations that may have no clear biological significance (i.e., they may not occur within a gene or may not have a detectable effect on gene activity) but have been shown to have a statistically significant correlation with a disease or a particular physiological condition. For example, a variation may frequently be detected in individuals with heart disease even though the reason for the correlation between the variation and the disease may be entirely mysterious.
Do you think parents should be able to order such a test for their children? What if the test indicates that a child is at risk for a disease for which there is no known cure?

Answer 1

The test within the case study shouldn't be ordered by parents. First of all, no child wants to be treated as a guinea pig. If a parent wants to know the status of their child's health, they should take them to a nearby physician. Although parents may trust the at-home genetic test and request an exam, the results may not be correct. A lot of at-home test have a high possibility of being faulty.
If the test indicates that a child is at risk for a disease for which there is no known cure, the best advice would be to tell the parents to seek a second opinion. The company may have made a mistake while testing. To ensure that the results obtained are accurate, the best thing to do is seek a second opinion.

Question 2

In what years did the publicly funded Human Genome Project begin and end? What were the scientific goals of the HGP?

Answer 2

The publicly funded Human Genome Project started in October of 1990. The human genome was published in 2003, but many other species have since been sequenced. The scientific goals of the Human Genome Project were to identify, sequence, map, and catalogue the gene coding regions of the human genome and identify their functions. Although the name singles out humans, other species where targeted as well.

Question 3

How many nucleotides does the human genome contain?

Answer 3

Nucleotides are monomers of DNA (deoxyribonucleic acid). There are four in DNA; adenine, cytosine, guanine, and thymine. The order of nucleotides creates a sequence. The number of nucleotides in a human genome is about 3.2 billion.

Question 4

Which of the following best describes the process of DNA sequencing?

A) DNA is separated on a gel, and the different bands are labeled with fluorescent nucleotides and scanned with a laser.
B) A laser is used to fluorescently label the nucleotides present within the DNA, the DNA is run on a gel, and then the DNA is broken into fragments.
C) Nucleotides are scanned with a laser and incorporated into the DNA that has been separated on a gel, and then the DNA is amplified with PCR.
D) Fragments of DNA are produced in a reaction that labels them with any of four different fluorescent dyes, and the fragments then are run on a gel and scanned with a laser.
E) DNA is broken down into its constituent nucleotides, and the nucleotides are then run on a gel and purified with a laser.

Question 5

Which of the following is NOT an activity carried out in the field of bioinformatics?

A) collecting and storing DNA sequence information produced by various genome sequencing projects
B) analyzing genome sequences to determine the location of genes
C) determining the three-dimensional structure of proteins
D) comparing genomes of different species
E) none of these

Question 6

How did the sequencing strategy used by the Human Genome Project differ from that used by Celera Corporation?

Question 7

Once an organism's genome has been sequenced, how do geneticists usually go about trying to pinpoint the locations of the genes?

Question 8

What percentage of the DNA in the genome actually corresponds to genes? How much is actually protein-coding exons? What makes up the rest?

Question 9

James sees an online ad for an at-home genetic test that promises to deliver personalized nutritional advice based on an individual's genetic profile. The company can test for genetic variations, the advertisement states, that predispose individuals to developing health conditions such as heart disease and bone loss or that affect how they metabolize certain foods. If such variations are detected, the company can provide specific nutritional advice that will help counteract their effects. Always keen to take any steps available to ensure the best possible health for their family, James and his wife (Sally) decide that they both should be tested, as should their 11-year-old daughter (Patty). They order three kits.
Once the kits arrive, the family members use cotton swabs to take cell samples from their cheeks and place the swabs in individually labeled envelopes. They mail the envelopes back to the company, along with completed questionnaires regarding their diets. Four weeks later, they receive three individual reports detailing the test results and providing extensive guidelines about what foods they should eat. Among the results is the finding that James has a particular allele in a gene that may make him vulnerable to the presence of free radicals in his cells. The report suggests that he increase his intake of antioxidants, such as vitamins C and E, and highlights a number of foods that are rich in those vitamins. The tests also show that Sally has several genetic variations that indicate that she may be at risk for elevated bone loss. The report recommends that she try to minimize this possibility by increasing her intake of calcium and vitamin D and lists a number of foods she could emphasize in her diet. Finally, the report shows that Patty has a genetic variation that may mean that she has a lowered ability to metabolize saturated fats, putting her at risk for developing heart disease. The report points to ways in which she can lower her intake of saturated fats and lists various types of foods that would be beneficial for her.
A number of companies now offer genetic-testing services, promising to deliver personalized nutritional or other advice based on people's genetic profiles. Generally, these tests fall into two different categories, with individual companies offering unique combinations of the two. The first type of test detects alleles of known genes that encode proteins that play an established role in, for example, counteracting free radicals in cells or in building up bone. In such cases, it is easy to see why individuals carrying alleles that may encode proteins with lower levels of activity may be more vulnerable to free radicals or more susceptible to bone loss.
A second type of test examines genetic variations that may have no clear biological significance (i.e., they may not occur within a gene or may not have a detectable effect on gene activity) but have been shown to have a statistically significant correlation with a disease or a particular physiological condition. For example, a variation may frequently be detected in individuals with heart disease even though the reason for the correlation between the variation and the disease may be entirely mysterious.
Do James and Sally have any guarantees that the tests and recommendations are scientifically valid?

Question 10

When the human genome sequence was finally completed, scientists were surprised to discover that the genome contains far fewer genes than expected. How many genes are present in the human genome? Scientists have also found that there are many more different kinds of proteins in human cells than there are different genes in the genome. How can this be explained?

Question 11

Who Owns Your Genome?
John Moore, an engineer working on the Alaska oil pipeline, was diagnosed in the mid-1970s with a rare and fatal form of cancer known as hairy cell leukemia. This disease causes overproduction of one type of white blood cell known as a T lymphocyte. Moore went to the UCLA Medical Center for treatment and was examined by Dr. David Golde, who recommended that Moore's spleen be removed in an attempt to slow down or stop the cancer. For the next 8 years, John Moore returned to UCLA for checkups. Unknown to Moore, Dr. Golde and his research assistant applied for and received a patent on a cell line and products of that cell line derived from Moore's spleen. The cell line, named Mo, produced a protein that stimulates the growth of two types of blood cells that are important in identifying and killing cancer cells. Arrangements were made with Genetics Institute, a small start-up company, and then Sandoz Pharmaceuticals, to develop the cell line and produce the growth-stimulating protein. Moore found out about the cell line and its related patents and filed suit to claim ownership of his cells and asked for a share of the profits derived from the sale of the cells or products from the cells. Eventually, the case went through three courts, and in July 1990-11 years after the case began-the California Supreme Court ruled that patients such as John Moore do not have property rights over any cells or tissues removed from their bodies that are used later to develop drugs or other commercial products.
This case was the first in the nation to establish a legal precedent for the commercial development and use of human tissue. The National Organ Transplant Act of 1984 prevents the sale of human organs. Current laws allow the sale of human tissues and cells but do not define ownership interests of donors. Questions originally raised in the Moore case remain largely unresolved in laws and public policy. These questions are being raised in many other cases as well. Who owns fetal and adult stem-cell lines established from donors, and who has ownership of and a commercial interest in diagnostic tests developed through cell and tissue donations by affected individuals? Who benefits from new genetic technologies based on molecules, cells, or tissues contributed by patients? Are these financial, medical, and ethical benefits being distributed fairly? What can be done to ensure that risks and benefits are distributed in an equitable manner?
Gaps between technology, laws, and public policy developed with the advent of recombinant DNA technology in the 1970s, and in the intervening decades, those gaps have not been closed. These controversies are likely to continue as new developments in technology continue to outpace social consensus about their use.
Should the physicians at UCLA have told Mr. Moore that his cells and its products were being commercially developed?

Question 12

One unexpected result of the sequencing of the human genome was the finding that mutations in a single gene can be responsible for multiple distinct disorders. For example, mutations in the RET gene can cause two different types of multiple endocrine neoplasias, familial medullary thyroid carcinoma, and Hirschsprung disease. How do you think mutations in a single gene can have such diverse effects?

Question 13

The gene controlling ABO blood type and the gene underlying nail-patella syndrome are said to show linkage. What does that mean in terms of their relative locations in the genome? What does it mean in terms of how the two traits are inherited with respect to each other?

Question 14

Sequence comparison studies revealed that the product of the CFTR (cystic fibrosis) gene has a strong similarity to proteins known to be involved in:

A) transcription
B) translation
C) transport of ions across the cell membrane
D) mRNA splicing
E) movement of proteins across the Golgi membrane

Question 15

James sees an online ad for an at-home genetic test that promises to deliver personalized nutritional advice based on an individual's genetic profile. The company can test for genetic variations, the advertisement states, that predispose individuals to developing health conditions such as heart disease and bone loss or that affect how they metabolize certain foods. If such variations are detected, the company can provide specific nutritional advice that will help counteract their effects. Always keen to take any steps available to ensure the best possible health for their family, James and his wife (Sally) decide that they both should be tested, as should their 11-year-old daughter (Patty). They order three kits.
Once the kits arrive, the family members use cotton swabs to take cell samples from their cheeks and place the swabs in individually labeled envelopes. They mail the envelopes back to the company, along with completed questionnaires regarding their diets. Four weeks later, they receive three individual reports detailing the test results and providing extensive guidelines about what foods they should eat. Among the results is the finding that James has a particular allele in a gene that may make him vulnerable to the presence of free radicals in his cells. The report suggests that he increase his intake of antioxidants, such as vitamins C and E, and highlights a number of foods that are rich in those vitamins. The tests also show that Sally has several genetic variations that indicate that she may be at risk for elevated bone loss. The report recommends that she try to minimize this possibility by increasing her intake of calcium and vitamin D and lists a number of foods she could emphasize in her diet. Finally, the report shows that Patty has a genetic variation that may mean that she has a lowered ability to metabolize saturated fats, putting her at risk for developing heart disease. The report points to ways in which she can lower her intake of saturated fats and lists various types of foods that would be beneficial for her.
A number of companies now offer genetic-testing services, promising to deliver personalized nutritional or other advice based on people's genetic profiles. Generally, these tests fall into two different categories, with individual companies offering unique combinations of the two. The first type of test detects alleles of known genes that encode proteins that play an established role in, for example, counteracting free radicals in cells or in building up bone. In such cases, it is easy to see why individuals carrying alleles that may encode proteins with lower levels of activity may be more vulnerable to free radicals or more susceptible to bone loss.
A second type of test examines genetic variations that may have no clear biological significance (i.e., they may not occur within a gene or may not have a detectable effect on gene activity) but have been shown to have a statistically significant correlation with a disease or a particular physiological condition. For example, a variation may frequently be detected in individuals with heart disease even though the reason for the correlation between the variation and the disease may be entirely mysterious.
Do you think that companies should be allowed to market such tests directly to the public, or do you believe that only a physician should be able to order them?

Question 16

You join a laboratory that studies a rare genetic disorder that causes affected individuals to have unusually fast-growing, bright green hair. You are joining the lab at a fortuitous moment, as the gene causing the disorder has just been cloned. Despite this breakthrough, however, it is still unclear what the function of the gene is, and the lab director asks you for suggestions about how to go about trying to determine this. What do you recommend?

Question 17

Who Owns Your Genome?
John Moore, an engineer working on the Alaska oil pipeline, was diagnosed in the mid-1970s with a rare and fatal form of cancer known as hairy cell leukemia. This disease causes overproduction of one type of white blood cell known as a T lymphocyte. Moore went to the UCLA Medical Center for treatment and was examined by Dr. David Golde, who recommended that Moore's spleen be removed in an attempt to slow down or stop the cancer. For the next 8 years, John Moore returned to UCLA for checkups. Unknown to Moore, Dr. Golde and his research assistant applied for and received a patent on a cell line and products of that cell line derived from Moore's spleen. The cell line, named Mo, produced a protein that stimulates the growth of two types of blood cells that are important in identifying and killing cancer cells. Arrangements were made with Genetics Institute, a small start-up company, and then Sandoz Pharmaceuticals, to develop the cell line and produce the growth-stimulating protein. Moore found out about the cell line and its related patents and filed suit to claim ownership of his cells and asked for a share of the profits derived from the sale of the cells or products from the cells. Eventually, the case went through three courts, and in July 1990-11 years after the case began-the California Supreme Court ruled that patients such as John Moore do not have property rights over any cells or tissues removed from their bodies that are used later to develop drugs or other commercial products.
This case was the first in the nation to establish a legal precedent for the commercial development and use of human tissue. The National Organ Transplant Act of 1984 prevents the sale of human organs. Current laws allow the sale of human tissues and cells but do not define ownership interests of donors. Questions originally raised in the Moore case remain largely unresolved in laws and public policy. These questions are being raised in many other cases as well. Who owns fetal and adult stem-cell lines established from donors, and who has ownership of and a commercial interest in diagnostic tests developed through cell and tissue donations by affected individuals? Who benefits from new genetic technologies based on molecules, cells, or tissues contributed by patients? Are these financial, medical, and ethical benefits being distributed fairly? What can be done to ensure that risks and benefits are distributed in an equitable manner?
Gaps between technology, laws, and public policy developed with the advent of recombinant DNA technology in the 1970s, and in the intervening decades, those gaps have not been closed. These controversies are likely to continue as new developments in technology continue to outpace social consensus about their use.
Do you think that donors or patients who provide cells and/or tissues should retain ownership of their body parts or should share in any financial benefits that might derive from their use in research or commercial applications?

Question 18

Obese individuals have a gut microbiome very different from nonobese individuals, which alters lipid metabolism. Do you think it might be possible to treat conditions such as obesity by manipulating the microbiome? How would you get living microorganisms into the gut for treatment?

Question 19

Hemophilia and color blindness are both recessive conditions caused by genes on the X chromosome. To calculate the recombination frequency between the two genes, you draw a large number of pedigrees that include grandfathers with both hemophilia and color blindness, their daughters (who presumably have one chromosome with two normal alleles and one chromosome with two mutant alleles), and the daughters' sons. Analyzing all the pedigrees together shows that 25 grandsons have both color blindness and hemophilia, 24 have neither of the traits, 1 has color blindness only, and 1 has hemophilia only. How many centimorgans (map units) separate the hemophilia locus from the locus for color blindness?

Question 20

How does proteomics differ from genomics? What kinds of information can proteomics provide that is not available from genomics studies?

Question 21

James sees an online ad for an at-home genetic test that promises to deliver personalized nutritional advice based on an individual's genetic profile. The company can test for genetic variations, the advertisement states, that predispose individuals to developing health conditions such as heart disease and bone loss or that affect how they metabolize certain foods. If such variations are detected, the company can provide specific nutritional advice that will help counteract their effects. Always keen to take any steps available to ensure the best possible health for their family, James and his wife (Sally) decide that they both should be tested, as should their 11-year-old daughter (Patty). They order three kits.
Once the kits arrive, the family members use cotton swabs to take cell samples from their cheeks and place the swabs in individually labeled envelopes. They mail the envelopes back to the company, along with completed questionnaires regarding their diets. Four weeks later, they receive three individual reports detailing the test results and providing extensive guidelines about what foods they should eat. Among the results is the finding that James has a particular allele in a gene that may make him vulnerable to the presence of free radicals in his cells. The report suggests that he increase his intake of antioxidants, such as vitamins C and E, and highlights a number of foods that are rich in those vitamins. The tests also show that Sally has several genetic variations that indicate that she may be at risk for elevated bone loss. The report recommends that she try to minimize this possibility by increasing her intake of calcium and vitamin D and lists a number of foods she could emphasize in her diet. Finally, the report shows that Patty has a genetic variation that may mean that she has a lowered ability to metabolize saturated fats, putting her at risk for developing heart disease. The report points to ways in which she can lower her intake of saturated fats and lists various types of foods that would be beneficial for her.
A number of companies now offer genetic-testing services, promising to deliver personalized nutritional or other advice based on people's genetic profiles. Generally, these tests fall into two different categories, with individual companies offering unique combinations of the two. The first type of test detects alleles of known genes that encode proteins that play an established role in, for example, counteracting free radicals in cells or in building up bone. In such cases, it is easy to see why individuals carrying alleles that may encode proteins with lower levels of activity may be more vulnerable to free radicals or more susceptible to bone loss.
A second type of test examines genetic variations that may have no clear biological significance (i.e., they may not occur within a gene or may not have a detectable effect on gene activity) but have been shown to have a statistically significant correlation with a disease or a particular physiological condition. For example, a variation may frequently be detected in individuals with heart disease even though the reason for the correlation between the variation and the disease may be entirely mysterious.
What kinds of regulations, if any, should be in place to ensure that the results of these tests are not abused?

Question 22

How did the Human Genome Project attempt to deal with the social and ethical issues that were bound to arise from the sequencing of the human genome?

Question 23

Before the advent of recombinant DNA technology, why was it so difficult for geneticists to map human genes by using pedigrees? How did recombinant DNA technology help move things forward?